15307-78-5Relevant articles and documents
One drop chemical derivatization - DESI-MS analysis for metabolite structure identification
Lubin, Arnaud,Cabooter, Deirdre,Augustijns, Patrick,Cuyckens, Filip
, p. 871 - 878 (2015)
Structural elucidation of metabolites is an important part during the discovery and development process of new pharmaceutical drugs. Liquid Chromatography (LC) in combination with Mass Spectrometry (MS) is usually the technique of choice for structural identification but cannot always provide precise structural identification of the studied metabolite (e.g. site of hydroxylation and site of glucuronidation). In order to identify those metabolites, different approaches are used combined with MS data including nuclear magnetic resonance, hydrogen/deuterium exchange and chemical derivatization followed by LC-MS. Those techniques are often time-consuming and/or require extra sample pre-treatment. In this paper, a fast and easy to set up tool using desorption electrospray ionization-MS for metabolite identification is presented. In the developed method, analytes in solution are simply dried on a glass plate with printed Teflon spots and then a single drop of derivatization mixture is added. Once the spot is dried, the derivatized compound is analyzed. Six classic chemical derivatizations were adjusted to work as a one drop reaction and applied on a list of compounds with relevant functional groups. Subsequently, two successive reactions on a single spot of amoxicillin were tested and the methodology described was successfully applied on an in vitro incubated alprazolam metabolite. All reactions and analyses were performed within an hour and gave useful structural information by derivatizing functional groups, making the method a time-saving and efficient tool for metabolite identification if used in addition or in some cases as an alternative to common methods.
Synthetic Strategies for the Modification of Diclofenac
Schmidt, Stephan,Hanelt, Sven,Canitz, Carsten,Hoffmann, Holger,Garbe, Leif-Alexander,Schneider, Rudolf J.
, p. 1984 - 1989 (2017)
For many heterogeneous sensor applications as well as the synthesis of hapten antigens to produce antibodies, protein conjugates of the target substance are essential. A requirement is that the target substance already offers or is modified to contain a functionality that allows for coupling to a protein, that is, an amino acid residue. Ideally, to avoid shielding of the compound by the carrier protein, a sufficient distance to the protein surface should be provided. With its carboxyl function diclofenac (DCF) allows for direct binding to lysine residues after in situ synthesis of the NHS ester. One problem is that diclofenac as free acid tends to autocondensation, which results in low yields. Here we describe the 'insertion' of a C6 spacer via synthesis of the amide with 6-aminohexanoic acid. To carry out the reaction in solution, first the methyl ester of the amino acid had to be produced. Due to otherwise low yields and large cleaning efforts, solid-phase synthesis on Fmoc Ahx Wang resin is recommended. The crude product is mainly contaminated by cleavage products from the resin which were removed by chromatography. The structure of the highly pure hapten was completely determined by nuclear magnetic resonance (NMR) spectroscopy.
Synthesis of Novel Diclofenac Hydrazones: Molecular Docking, Anti-Inflammatory, Analgesic, and Ulcerogenic Activity
Al-Dhfyan, Abdullah,Al-Omar, Mohamed A.,Al-Tuwajiri, Hanaa M.,Alsaif, Nawaf A.,Bhat, Mashooq A.,Naglah, Ahmed M.
, (2020/12/28)
This study was aimed to design novel diclofenac hydrazones having anti-inflammatory and analgesic activity with gastric sparing effect. A new series of 2-[2-(2,6-dichloroanilino)phenyl]-N'-[(substituted phenyl) methylidene] acetohydrazide derivatives (1-14) were synthesized and evaluated for their anti-inflammatory, analgesic, and ulcerogenic activity. The compounds were identified and confirmed by elemental analysis and spectral data. During anti-inflammatory activity by carrageenan-induced paw edema method, compounds (2, 3, 7, 8, 11, and 13) were found to be most promising. Compounds 3, 8, and 13 have been found to have significant analgesic activity compared to the reference drug diclofenac in analgesic activity by both the hot plate method and acetic acid-induced writhing method. The compounds which presented highly significant anti-inflammatory and analgesic activity were further tested for their ulcerogenic activity. Compounds 3 and 8 showed maximum ulcerogenic reduction activities. Compound 8 was found to have LD50 of 168 mg/kg. Compound 8 with 3,5-dimethoxy-4-hydroxyphenyl substitution was found to be the most promising anti-inflammatory and analgesic agent with gastric sparing activity. Molecular docking of compounds was performed for COX-1/COX-2 binding site. Lead compound 8 showed better binding affinities of -9.4 kJ/mol with both COX-1 and COX-2 as compared to the standard drug, diclofenac with binding affinities of -6.6 kJ/mol and -8.1 kJ/mol for COX-1 and COX-2, respectively.
Synthetic method of diclofenac sodium
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Paragraph 0017-0026, (2019/04/26)
The invention relates to a synthetic method of diclofenac sodium, and a synthetic route thereof, in a compound A, X is Cl, Br or I, M is Me, Et or Pro, a catalyst used for the condensation reaction isCuI, CuBr, CuBR2 or CuF2, and a sugar ligand used for the reaction is D-glucosamine hydrochloride, glucose, chitosan, D-galactose and L- arabinose. The method for synthesizing diclofenac sodium according to the invention has a purity of more than 98% and a total yield of two steps of up to 90% or more. According to the synthetic method of the diclofenac sodium, the purity of the product is up tomore than 98%, the total yield of two steps is up to more than 90%, and the yield is high; and D-glucosamine hydrochloride is adopted to replace ligands such as 8-hydroxyquinoline and the like which are high in price and large in environmental pollution, the pollution to the environment is reduced while the production cost is reduced.
